In-silico screening of potential inhibitors of HMGCoA reductase and Lanosterol synthase, key enzymes in cholesterol biosynthesis pathway

Hyperlipidemia is elevated level of lipids or lipoproteins in our body. Cholesterol is a major lipid particle circulating in our body. Cholesterol synthesis takes place in liver and this biosynthesis pathway is called Mevalonate pathway. Cholesterol is the end product of this Mevalonate pathway. Several enzymes play a role in the Cholesterol biosynthesis. Enzymes like HMGCoA synthase, HMGCoA reductase, Farnesyl PP synthase, Lanosterol synthase, Squalene synthase. This cholesterol is mainly responsible for several health effects especially Coronary heart diseases, atherosclerosis etc. So now in order to prevent the cholesterol synthesis in our body, we need to find potent inhibitors against the above enzymes and there after modify them as drugs. In this study, two enzymes HMGCoA reductase and Lanosterol synthase were targeted. For our docking study, we used Arguslab, Mgl tools, Autodock vina softwares for obtaining binding energies of protein and ligands. We search for already available drugs acting against HMGCoA reductase called Statins. We obtained binding energy results with NADH, PRAVASTATIN, LOVASTATIN, CERIVASTATIN, SIMVASTATIN, FLUVASTATIN, BEZAFIBRATE and note them as POSITIVE CONTROL 1. Then we dock HMGCoA reductase with natural molecules and compare them with positive control 1. In the next step, we targeted Lanosterol Synthase with available Quinuclidine inhibitors and results obtained was noted as POSITIVE CONTROL 2. Now we cross docked Lanosterol synthase with previous natural ligands and compared them with Positive control 2. We later found the toxicity and druglikeness of all inhibitors used against both the targets. We found two natural molecules APIGENIN and NARINGENIN which showed best binding energy results against both the targets. Both Apigenin and Naringenin act as suitable inhibitors against HMGCoA reductase and Lanosterol synthase inhibiting at two places along the Mevalonate pathway

City Profile: Hyderabad

The report documents the urban transformation of Hyderabad, from its founding in the sixteenth century to its present day positioning as a global centre, especially for Information Technology (IT)- and Life Sciences-based industries. Locating the city’s contemporary experience of climate in this history is important. While the city has been a key cultural and economic centre since its founding, its transformation into a global centre has dramatically altered the city’s spatial and demographic characteristics, and the texture of its built environment. Such transformations have profound implications for how heat is experienced and responded to in the city

Towards a climate-health approach in Indian healthcare: Perspectives of specialist doctors on health impacts of extreme heat in Hyderabad

Introduction: Climate change impacts human health by exacerbating existing vulnerabilities to communicable and non-communicable diseases and creating new ones. Consequently, there has been increasing recognition of the need for a dedicated focus on ‘climate health’ in medical education and the healthcare profession globally. In this study, we explored the perspectives of doctors on the impact of heat on human health in Hyderabad, India and how a climate health approach can be adopted across Indian healthcare. Methods: A global literature review on climate health broadly, and heat health specifically was carried out. Based on our analysis of the literature, we developed an interview questionnaire and conducted semi-structured interviews with 16 specialist physicians in order to understand their perspectives on the impacts of heat on human health in the region of Hyderabad and institutional transformations necessary to better address questions of heat health. Interview findings were interpreted against extant research on climate health. Results: Climate health and heat-health challenges are aggravating globally, and the doctors perceive that the Hyderabad region is no exception. While efforts are underway to operationalize a climate health approach in healthcare systems in countries of the Global North, such an orientation is almost absent from the context of Indian medical education and healthcare. Conclusion: Impacts of climate change and heat on human health are becoming more apparent in the Hyderabad region. This suggests a strong need to incorporate greater attention to climate health and heat health as part of medical education and the healthcare system in India. Funding: This research has been conducted as part of the “Cool Infrastructures: Life with Heat in the Offgrid City” project funded by the Economic and Social Research Council (ESRC), UK (Award No: ES/T008091/1)